1. Field of the Invention
The invention is directed to a rehydration formulation for the replacement of electrolytes and enhanced water retention. In particular, the invention relates to a frozen rehydration formulation and unique delivery system therefor. The delivery system provides a convenient and effective vehicle for administering therapeutic agents in a way that is readily acceptable to children.
2. Description of Related Art
It is known that both negative energy balance and muscle catabolism are consequences of physiological stress that often accompanies protein calorie malnutrition, strenuous physical exercise, physical trauma, burn injury, surgical trauma, malnutrition, maldigestion, malabsorption, hyperthyroidism, chemotherapy, radiation therapy, anorexia, cachexia, short bowel syndrome, old age, and sepsis. It is also known that maintaining a positive metabolic energy balance can help to alleviate such problems and also has a sparing effect on muscle catabolism that occurs during strenuous physical exertion.
In order to properly combat the symptoms of physiological stress, it is essential that appropriate amounts of nutrients be available to replace those which are utilized or lost. Proper food energy (available calories), hydration and mineral bioavailability are essential to enable the body to maintain a proper balance in both intracellular and extracellular fluids and to also maintain proper enzymatic functioning, pH balance, osmotic pressure, and the like.
Nutritional supplements including liquid endurance and rehydration compositions are well known in the art. Rehydration solutions are conventionally used to replace electrolytes lost during vomiting and diarrhea, as well as during strenuous exercise. Diarrhea in particular can be a severe disease, especially in infants and young children, and can often result in death. Diarrhea is common amongst travellers and those exposed to low standards of hygiene. Diarrhea frequently involves colonization of the small intestine with enteropathogenic strains of E. coli which produce heat stable and/or heat labile enterotoxins. Related enterotoxins are produced by other enteropathogens such as cholera, and also cause diarrhea. These enterotoxins stimulate fluid secretion in the gut lumen and cause diarrhea. Associated fluid loss may lead to death.
In cases of severe dehydration corrective parenteral therapy is often necessary. In cases of mild to moderate dehydration oral rehydration solutions provide a safe, economical alternative to intravenous therapy. In order to promote rehydration, it is necessary to provide a source of energy and also a source of dietary supplements which can be directed to proper cellular and/or tissue sites in the course of the rehydration process. Oral rehydration solutions used in oral rehydration therapy generally consist of a mixture of electrolytes and a carbohydrate component such as glucose or sucrose. Examples of commercially available oral electrolyte replacement and/or maintenance solutions include Rehydrolyte.RTM. and Pedialyte.RTM., manufactured by Ross Laboratories, Columbus, Ohio, and Magonate.RTM. Liquid, manufactured by Fleming and Company, Fenton, Mo.
The development of oral rehydration therapy for acute diarrheal diseases of infancy and childhood has significantly reduced related morbidity and mortality, particularly in less developed countries where it constitutes the primary mode of therapy. The World Health Organization (WHO) currently recommends that oral rehydration solutions for treatment of acute diarrheal therapy contain 90 mEq sodium/liter, 20 mEq potassium/liter, 80 mEq chloride/liter, 30 mEq citrate/liter or 30 mEq bicarbonate/liter, and 110 mmol glucose/liter. Glucose is recommended as the carbohydrate component in such oral rehydration solutions. Glucose enhances the membrane transport of sodium which in turn enables rapid uptake of water. The WHO formulation has been shown to decrease morbidity and mortality.
Substitution of other carbohydrates for glucose in WHO-type formulations has been investigated. Lebenthal et al (J. Pediatrics, 1983, 103:29-34) studied the effect of three corn syrup sugars (dextrins) containing glucose polymers of varying lengths having dextrose equivalents of 10, 15 and 24 and determined they were suitable as the sole carbohydrate source in oral rehydration therapy. It has also been established that oral rehydration solutions in which rice and other food sources of starch are substituted for glucose are effective as reported by Carpenter et aL (New England J. Med., 1988, 319:1346-1348). Rice-based oral rehydration solutions containing from 3 to 5% rice and having electrolyte levels corresponding to conventional WHO formulations, have been found to be effective as reported by Patra et al. (Archives of Disease in Childhood, 1982, 57:910-912), Molla et al (The Lancet, 1982, pp. 1317-1319), El Mougi et al (Journal of Pediatric Gastroenterology and Nutrition, 1988, 7:572-576), and Molla et al. (Journal of Gastroenterology and Nutrition, 1989, 8:81-84). U.S. Pat. No. 5,096,894 discloses an oral rehydration solution comprising a mixture of the required electrolytes and rice dextrin containing a distribution of short chain glucose polymers consisting of 50-90% 2 to 6 glucose units.
U.S. Pat. No. 5,270,297 discloses an oral rehydration solution including a blend of simple sugars, more complex carbohydrates and minerals, in particular magnesium. Other ingredients include electrolyte ions (e.g., potassium, sodium, chloride), vitamins, anabolic nutrients, and other minerals such as calcium. The magnesium and calcium are provided in the form of amino acid chelates to facilitate rehydration and promote endurance.
U.S. Pat. Nos. 4,505,926, 4,539,319, 4,558,063 and 4,594,195 disclose various oral rehydration solutions containing pharmaceutically active ingredients (i.e., drugs) for treatment of enterotoxin induced diarrhea and prevention of death from enteropathogenic E. coli infection of the gastro-intestinal tract. Drugs incorporated into these prior art rehydration solutions include quaternary aminophenyliminoimidazolidines, 2-aminoimidazoline derivative, and 5,6,7,8-tetrahydro-naphonitrile intermediates.
U.S. Pat. No. 4,942,042 is directed to an anti-diarrhea composition comprising an absorptive component and an electrolyte/sugar component. The absorptive material is a thermally activated, finely powdered, hydrous magnesium aluminum silicate clay capable of absorbing pathogenic intestinal bacteria. The absorptive material is preferably also capable of absorbing diarrhea-associated viruses, intestinal toxins and gases. Suitable absorptive materials are clays such as Smectite (Si.sub.8 Al.sub.4 O.sub.20 OH.sub.4). Other such clays are argillaceous clays. The electrolyte/sugar component contains a sodium salt, a potassium salt and a sugar. The composition is packaged in solid form and reconstituted by admixture with water prior to administration.
U.S. Pat. No. 5,192,551 discloses rehydration and infant nutrient formulas containing a neutral glycolipid, in particular, gangliotetracosylceramide. The glycolipid binds enteric virus, e.g., rotaviruses, which are pathogenic to humans. Rotaviruses are RNA viruses known to replicate in the intestinal epithelial cells of a wide range of animal species, including humans.
Electrolytes generally have a disagreeable taste. As such, rehydration solutions are often difficult to administer, especially to young children. While oral electrolyte maintenance and replenishing solutions for infants and children are available, such as Fruit-Flavored Pedialyte.RTM. manufactured by Ross Laboratories, Columbus, Ohio, there remains a need in the art for an effective rehydration formula which is readily consumed by children.